Efficacy and Safety of Riociguat in Patients With Systemic Sclerosis

Overview

About this study

To investigate if Riociguat is effective in the treatment of systemic sclerosis

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

Men or women aged 18 years and older
Systemic sclerosis, as defined by ACR/EULAR (American College of Rheumatology/European League Against Rheumatism) 2013 criteria
dcSSc (diffuse cutaneous systemic sclerosis) according to the LeRoy criteria, ie, skin fibrosis proximal to the elbows and knees in addition to acral fibrosis
Disease duration of ≤ 18 months (defined as time from the first non−Raynaud's phenomenon manifestation)
≥ 10 and ≤ 22 mRSS (modified Rodnan skin score) units at the screening visit
FVC (forced vital capacity) ≥ 45% of predicted at screening
DLCO (diffusion capacity of the lung for carbon monoxide) ≥ 40% of predicted (hemoglobin-corrected) at screening
Negative serum pregnancy test in a woman of childbearing potential at the screening visit
Women of childbearing potential must agree to use adequate contraception when sexually active. "Adequate contraception" is defined as any combination of at least 2 effective methods of birth control, of which at least 1 is a physical barrier (e.g. condom with hormonal contraception like implants or combined oral contraceptives, condom with intrauterine devices). This applies since signing of the informed consent form until 30 (+5) days after the last study drug administration.

Exclusion Criteria:

Limited cutaneous SSc (systemic sclerosis) at screening
Major surgery (including joint surgery) within 8 weeks prior to screening
Hepatic insufficiency classified as Child-Pugh C
Patients with isolated AST or ALT >3xULN or bilirubin >2xULN can be included in the trial under the condition of additional monitoring during the trial
Estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73m2 (Modification of Diet in Renal Disease formula) or on dialysis at the screening visit. Patients entering the trial with eGFR 15-29 mL/min/1.73m2 will be undergo additional monitoring of renal function
Any prior history of renal crisis
Sitting SBP (systolic blood pressure) < 95 mmHg at the screening visit
Sitting heart rate < 50 beats per minute (BPM) at the screening visit
Left ventricular ejection fraction < 40% prior to screening
Any form of pulmonary hypertension as determined by right heart catheterization
Pulmonary disease with FVC < 45% of predicted or DLCO (hemoglobin-corrected) < 40% of predicted at screening
Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization
Not permitted prior and concomitant medication
Pregnant or breast feeding women
Women of childbearing potential not willing to use adequate contraception and not willing to agree to 4-weekly pregnancy testing from Visit 1 (first administration of study drug) onwards until 30 (+5) days after last study drug intake.

More information

Publications

RISE-SSc is a randomized, double-blind, placebo-controlled phase 2 study investigating the efficacy and safety of riociguat in patients with diffuse cutaneous systemic sclerosis (dcSSc). Based on positive results from riociguat trials in patients with pulmonary hypertension and chronic thromboembolic pulmonary hypertension in combination with the known antiproliferative and antifibrotic effects seen in animal models, patients with SSc may benefit from treatment with riociguat. Patients with SSc meeting the ACR/EULAR systemic sclerosis classification criteria with diffuse cutaneous SSc (dcSSc) subset per LeRoy criteria, and a disease duration of less than or equal to 18 months will be randomized to placebo or riociguat 0.5 mg (up-titrated to a maximum dose of 2.5 mg TID over 10 weeks) and maintained on therapy for a total of 52 weeks. During the first 10 weeks of the long-term extension phase, placebo subjects will be up-titrated on riociguat, and all patients will be followed for up to 6 years. The primary endpoint of change in modified Rodnan skin score (mRSS) from baseline will be assessed at 52 weeks, as will be secondary endpoints such as mRSS progression and regression rates, patient quality of life, digital ulcer burden, and change in forced vital capacity and carbon monoxide diffusing capacity. This review will further define the clinical rationale for the use of riociguat in the treatment of SSc and provide details on study protocol, design, and outcome reporting. Read More on PubMed

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